T cell modulation of COVID-19 disease

项目概要/摘要 2019年底出现的新型冠状病毒（SARS-CoV-2）迅速在世界各地传播 到目前为止，已经感染了数百万人，杀死了数十万人。这种病毒非常复杂， 大多数受感染的个体几乎没有明显的症状（尽管一些数据表明他们可能有 虽然是长期的伤害，但基本上是健康的。相比之下，一小部分感染者表现出 一系列严重的症状，包括肺炎，急性呼吸窘迫，凝血障碍，甚至 死亡轻度与重度症状的机制尚未完全了解，但免疫 机制似乎发挥了作用。因此，我们需要了解特定免疫细胞的作用， 了解疾病并正确治疗。特别感兴趣的是CD 8 T细胞（CTL）在疾病中的作用 结果。在这个项目中，我们将使用SARS-CoV-2感染的恒河猴模型来评估 CTL和其他CD 8+细胞在疾病中的重要性。在目标1中，我们将耗尽动物的所有细胞， CD 8a分子，包括CTL和NK细胞，并评估它们清除病毒的能力。在目标2中，我们 仅靶向CTL进行消耗并同样评估其重要性。在目标3中，我们将在实验室中使用细胞， 评估CTL如何与病毒感染的细胞相互作用。该项目将全面评估 CTL在COVID-19疾病中的重要性或对其的保护。

Project Summary/Abstract The novel coronavirus that emerged in late 2019, termed SARS-CoV-2, quickly spread throughout the world and has, to date, infected millions and killed hundreds of thousands. This virus is shockingly complex in that the majority of infected individuals show few overt symptoms (though some data suggest they may have lasting damage nonetheless) but are largely healthy. In contrast, a small fraction of infected individuals exhibit a range of serious symptoms including pneumonia, acute respiratory distress, clotting disorders, and even death. The mechanisms that underly mild versus severe symptoms are not fully understood but immune mechanisms appear to play a role. Thus, we need to understand the roles of particular immune cells in order to understand the disease and properly treat it. Of particular interest is the role of CD8 T cells (CTL) in disease outcome. In this project we will use the rhesus macaque model of SARS-CoV-2 infection to assess the importance of CTL and other CD8+ cells in disease. In aim 1, we will deplete animals of all cells that express the CD8a molecule, including CTL and NK cells, and assess their ability to clear the virus. In aim 2, we will target only CTL for depletion and likewise assess their importance. In aim 3, we will use cells in the lab to assess how CTL interact with virus infected cells. Together, this project will comprehensively assess the importance of CTL in COVID-19 disease or protection from it.